Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death
| العنوان: | Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death |
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| المؤلفون: | Jade Violleau, Stefan Kääb, Susan Bartkowiak, Richard Redon, Antoine Leenhardt, Hanno L. Tan, Jean-Baptiste Gourraud, Peter Weeke, Rachel Bastiaenen, Rianne Wolswinkel, Federica Dagradi, Vincent M. Christoffels, Jacob Tfelt-Hansen, Jean-Jacques Schott, Hervé Le Marec, Manfred Gessler, Françoise Gros, Pascale Guicheney, Julien Barc, Arthur A.M. Wilde, Simon Lecointe, Akihiko Nogami, Tohru Minamino, Sven Zumhagen, Margherita Torchio, Elijah R. Behr, Rainer Schimpf, Carol Ann Remme, Florence Kyndt, Lia Crotti, Yuka Mizusawa, Morten S. Olesen, Vincent Probst, Naoto Endo, Naomasa Makita, Eric Charpentier, Philippe Froguel, Arie O. Verkerk, Minoru Horie, Takeshi Aiba, Christian Dina, Peter J. Schwartz, Kanae Hasegawa, Floriane Simonet, Véronique Fressart, Seiko Ohno, Cornelia Wiese, Eric Schulze-Bahr, Stéphane Bézieau, Hiroshi Watanabe, Vincent Portero, Wataru Shimizu, Beverley Balkau, Martin Borggrefe, Britt M. Beckmann, Charles Antzelevitch, Bas J. Boukens, Dan M. Roden, Pierre Lindenbaum, Aurore Despres, David Weber, Olivier Lantieri, Connie R. Bezzina, Stéphanie Chatel, Ruben Coronel |
| المساهمون: | ACS - Amsterdam Cardiovascular Sciences, Cardiology, Medical Biology, Other departments, ARD - Amsterdam Reproduction and Development, Bezzina, C, Barc, J, Mizusawa, Y, Remme, C, Gourraud, J, Simonet, F, Verkerk, A, Schwartz, P, Crotti, L, Dagradi, F, Guicheney, P, Fressart, V, Leenhardt, A, Antzelevitch, C, Bartkowiak, S, Borggrefe, M, Schimpf, R, Schulze-Bahr, E, Zumhagen, S, Behr, E, Bastiaenen, R, Tfelt-Hansen, J, Olesen, M, Kääb, S, Beckmann, B, Weeke, P, Watanabe, H, Endo, N, Minamino, T, Horie, M, Ohno, S, Hasegawa, K, Makita, N, Nogami, A, Shimizu, W, Aiba, T, Froguel, P, Balkau, B, Lantieri, O, Torchio, M, Wiese, C, Weber, D, Wolswinkel, R, Coronel, R, Boukens, B, Bézieau, S, Charpentier, E, Chatel, S, Despres, A, Gros, F, Kyndt, F, Lecointe, S, Lindenbaum, P, Portero, V, Violleau, J, Gessler, M, Tan, H, Roden, D, Christoffels, V, Le Marec, H, Wilde, A, Probst, V, Schott, J, Dina, C, Redon, R |
| المصدر: | Nature genetics, 45(9), 1044-1049. Nature Publishing Group |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Qrs Duration, Bioinformatics, Sodium Channels, NAV1.5 Voltage-Gated Sodium Channel, Sudden cardiac death, Genome-Wide Association, Mice, Atrial Gene-Expression, Basic Helix-Loop-Helix Transcription Factors, Odds Ratio, Brugada Syndrome, Brugada syndrome, Mice, Knockout, St-Segment Elevation, SECS-S/01 - STATISTICA, cardiovascular system, Cardiology, Chromosomes, Human, Pair 6, Female, Chromosomes, Human, Pair 3, medicine.medical_specialty, Bundle-Branch Block, BIO/18 - GENETICA, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Article, NAV1.8 Voltage-Gated Sodium Channel, Internal medicine, Genetic variation, Cardiac conduction, Genetics, medicine, Animals, Humans, Genetic Predisposition to Disease, cardiovascular diseases, HEY2, Alleles, Heart-Rate, Genetic Variation, Cardiac arrhythmia, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, medicine.disease, Qt Interval Duration, Repressor Proteins, Ventricular-Fibrillation, Pr Interval, Death, Sudden, Cardiac, Case-Control Studies, Conduction System, Genome-Wide Association Study, Rare disease |
| الوصف: | Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10(-68); rs9388451, P = 5.1 × 10(-17)) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10(-14)). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (Ptrend = 6.1 × 10(-81)). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development. Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases. |
| وصف الملف: | STAMPA |
| تدمد: | 1546-1718 1061-4036 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8578dbbe2ed8dd464bb8685a62569057Test https://doi.org/10.1038/ng.2712Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8578dbbe2ed8dd464bb8685a62569057 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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